cymegesolate
{{Short description|Chemical compound}}
{{Drugbox
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| IUPAC_name = [(3S,8R,9S,10R,13S,14S,17R)-17-Acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] 3-cyclopentylpropanoate
| image = Cymegesolate structure.svg
| width = 250px
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| routes_of_administration = By mouth
| class = Progestin; Progestogen; Progestogen ester
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 72648-88-5
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| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4D9TFH8PLX
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| PubChem = 126290
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| ChemSpiderID = 112247
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| synonyms = Cypionyl megestrol acetate; Megestrol acetate 3β-cypionate; Megestrol acetate 3β-cyclopentylpropionate; Progestin No. 1; Progestin I; Progestagen I; 17α-Acetoxy-6-dehydro-6-methylprogesterone 3β-cypionate; 17α-Acetoxy-6-methylpregna-4,6-diene-3,20-dione 3β-cypionate
| C=32 | H=46 | O=5
| SMILES = CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=C[C@H](CC4)OC(=O)CCC5CCCC5)C
| StdInChI_Ref =
| StdInChI = 1S/C32H46O5/c1-20-18-25-26(13-16-31(5)27(25)14-17-32(31,21(2)33)37-22(3)34)30(4)15-12-24(19-28(20)30)36-29(35)11-10-23-8-6-7-9-23/h18-19,23-27H,6-17H2,1-5H3/t24-,25+,26-,27-,30+,31-,32-/m0/s1
| StdInChIKey_Ref =
| StdInChIKey = WAHQVRCNDCHDIB-QZYSPNBYSA-N
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Cymegesolate (developmental code name Progestin No. 1), also known as cypionyl megestrol acetate or as megestrol acetate 3β-cypionate, is a progestin medication which was never marketed.{{cite journal | vauthors = De-Wei Z | title = Research activities in the field of oral contraceptives in the People's Republic of China | journal = Acta Obstetricia et Gynecologica Scandinavica Supplement | volume = 105 | pages = 51–60 | date = 1982 | pmid = 6952745 | doi = 10.3109/00016348209155319 | s2cid = 44858028 }}{{cite book| vauthors = Yang YC, Gu XG, Li SX |title=Proteins and Steroids in Early Pregnancy|year=1982|pages=335–342|doi=10.1007/978-3-642-67890-5_22|isbn=978-3-642-67892-9}}Chi-ming, L. (1983). New Long Acting Contraceptive Progestagen Studies on Synthesis of “Cymegesolate”[J]. Reproduction & Contraception, 4, 011.{{cite journal | vauthors = Yang YQ, Li SX, Gu XG | title = [Effect of progestin no. 1 (cymegesolate) on menstrual cycles and plasma levels of progesterone in rhesus monkeys] | language = zh | journal = Sheng Li Xue Bao | volume = 37 | issue = 4 | pages = 368–373 | date = August 1985 | pmid = 3837333 }}{{cite journal | vauthors = Wu JZ, Yun XJ, Wu MZ, Shen HY, Wang AL | title = [Clinical study of a long-acting progestogen contraceptive 3-cyclopentyl propionate of megestrol acetate (progestin no. 1)] | language = Chinese | journal = Sheng Zhi Yu Bi Yun = Reproduction and Contraception | volume = 3 | issue = 2 | pages = 36–38 | date = February 1983 | pmid = 12339176 | doi = | url = }}Xue-jing, W. J. Z. Y., & Mo-zhen, W. (1983). Clinical Study of a Long-Acting Progestogen Contraceptive 3-Cyclopentyl Propionate of Megestrol Acetate (Progestin No. 1)[J]. Reproduction & Contraception, 2, 009. It was developed in China in the late 1970s and early to mid 1980s for use as a hormonal contraceptive. The medication was formulated at a dose of 50–100 mg in combination with a "trace" dose of 0.25–0.5 mg quinestrol as a long-lasting, once-a-month combined oral contraceptive pill. This combination has been studied in 1,213 women across a total of 9,651 menstrual cycles, with contraceptive effectiveness of over 99.13% and "very few side effects." At the high dose (100 mg / 0.5 mg), it showed an anovulation rate of only about 60%, and instead mediated its contraceptive effects via a marked anti-implantation effect.
Chemistry
{{See also|Progestogen ester|List of progestogen esters}}
Cymegesolate, also known as megestrol acetate 3β-cypionate, as well as 17α-acetoxy-6-dehydro-6-methylprogesterone 3β-cyclopentylpropionate or 17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione 3β-cyclopentylpropionate, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone. It is the C3β cypionate (cyclopentylpropionate) ester of megestrol acetate. A closely related medication is acetomepregenol (mepregenol diacetate; also known as megestrol 3β,17α-diacetate), which, in contrast, has been marketed.{{cite journal | vauthors = Sidel'nikova VM, Demidova EM, Borisova I, Dondukova TM, Absava GI, Korkhov VV | title = [The use of acetomepegrenol in the therapy of threatened abortion] | language = ru | journal = Akusherstvo I Ginekologiia | issue = 9 | pages = 37–40 | date = September 1990 | pmid = 2278305 }}{{cite journal| vauthors = Grinenko GS, Popova EV, Korkhov VV, Lesik EA, Petrosyan MA, Topil'skaya NI |title=Synthesis and biological activity of 17α-acetoxy-3β-phenylpropionyloxy-6-methylpregna-4,6-dien-20-one|journal=Pharmaceutical Chemistry Journal|issn=1573-9031|pages=113–114|volume=34|issue=3|date=March 2000|doi=10.1007/BF02524577 |s2cid=44235508|quote=Note that 3,17-diacetoxy-6-methylpregna-4,6-dien-20-one (1b), a structural analog of compound 1a, is certified in Russia under the trade name acetomepregnol and recommended for therapeutic purposes in gynecological practice and as a contraceptive preparation in combination with estrogens [4].}}{{cite journal| vauthors = Mashkovskii MD |title=Eightieth Anniversary of the Drug Chemistry Center/All-Russian Pharmaceutical Chemistry Scientific Research Institute|journal=Pharmaceutical Chemistry Journal|issn=1573-9031|pages=677–680|volume=34|issue=12|doi=10.1023/A:1010416205068|date=December 2000|s2cid=24703856}}{{cite journal| vauthors = Sergeev PV, Rzheznikov VM, Korkhov VV, Grinenko GS, Semeikin AV, Mayatskaya EE, Samoilikov RV | display-authors = 6 |title=Investigation of the Gestagen Activity of 17α-acetoxy-3β-butanoyloxy-6-methylpregna-4,6-dien-20-one|journal=Pharmaceutical Chemistry Journal|issn=1573-9031|pages=358–360|volume=39|issue=7|doi=10.1007/s11094-005-0154-4 |date=July 2005|s2cid=35450212|quote=Gestagens are widely used in medicine as drugs for the treatment of breast and uterine tumors, endometriosis, uterine bleeding, and premenstrual syndrome, as a means of hormonal therapy and maintenance of pregnancy, and as contraceptives [1, 2]. In clinics, drugs of this group are represented by acetomepregenol (AMP), medroxyprogesterone acetate (MPA), levonorgestrel, progesterone, didrogesterone, etc. [1].}}